rs11465835

Variant names:

• chrX-154017226-C-A
• rs11465835
• NM_001569.4:c.910-159G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001569.4(IRAK1):​c.910-159G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 112,660 control chromosomes in the GnomAD database, including 26 homozygotes. There are 460 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.015 (26 hom., 460 hem., cov: 24)
• Consequence: IRAK1 NM_001569.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 0 publications found

Genes affected

IRAK1 (HGNC:6112): (interleukin 1 receptor associated kinase 1) This gene encodes the interleukin-1 receptor-associated kinase 1, one of two putative serine/threonine kinases that become associated with the interleukin-1 receptor (IL1R) upon stimulation. This gene is partially responsible for IL1-induced upregulation of the transcription factor NF-kappa B. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

IRAK1 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0148 (1672/112660) while in subpopulation AFR AF = 0.0513 (1593/31023). AF 95% confidence interval is 0.0493. There are 26 homozygotes in GnomAd4. There are 460 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001569.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAK1	NM_001569.4	MANE Select	c.910-159G>T		intron	N/A	NP_001560.2
	IRAK1	NM_001410701.1		c.988-159G>T		intron	N/A	NP_001397630.1
	IRAK1	NM_001025242.2		c.910-159G>T		intron	N/A	NP_001020413.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAK1	ENST00000369980.8	TSL:1 MANE Select	c.910-159G>T		intron	N/A	ENSP00000358997.3
	IRAK1	ENST00000393687.6	TSL:1	c.910-159G>T		intron	N/A	ENSP00000377291.2
	IRAK1	ENST00000369974.6	TSL:1	c.910-159G>T		intron	N/A	ENSP00000358991.2

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 1661 AN: 112606 Hom.: 26 Cov.: 24

Gnomad AFR AF: 0.0511

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00568

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000188

Gnomad OTH AF: 0.00527

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0148 AC: 1672 AN: 112660 Hom.: 26 Cov.: 24 AF XY: 0.0132 AC XY: 460 AN XY: 34818

African (AFR) AF: 0.0513 AC: 1593 AN: 31023

American (AMR) AF: 0.00568 AC: 61 AN: 10745

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3582

South Asian (SAS) AF: 0.00 AC: 0 AN: 2752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6233

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.000188 AC: 10 AN: 53240

Other (OTH) AF: 0.00520 AC: 8 AN: 1537

Alfa AF: 0.0108 Hom.: 19

Bravo AF: 0.0172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.90
DANN	Benign	0.38
PhyloP100		-0.37
PromoterAI		0.0036	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11465835; hg19: chrX-153282677;